Control of sensitivity to induction of apoptosis in myeloid leukemic cells by differentiation and bcl-2 dependent and independent pathways

Induction of differentiation in M1 myeloid leukemic cells by the
hematopoietic cytokines interleukin 6 and granulocyte-colony stimulating
factor, or by the glucocorticoid dexamethasone, was associated with
down-regulation of the apoptosis inhibiting gene bcl-2. The cytokine
treated leukemic cells showed an increased sensitivity to induction of
apoptotic cell death by the cancer chemotherapy compounds Adriamycin and
cytosine arabinoside and by heat shock and cycloheximide. Dibutyryl cyclic
AMP neither induced differentiation nor down-regulated bcl-2 expression,
but it sensitized the cells to induction of apoptosis by some of these
agents. Although dexamethasone induced differentiation and down-regulated
bcl-2 expression, it did not sensitize the cells to induction of apoptosis
and inhibited the apoptosis sensitizing effect of the cytokines and
dibutyryl cyclic AMP. Dexamethasone did not inhibit induction of apoptosis
by wild-type p53 or viability factor withdrawal. The apoptosis sensitizing
effect of the cytokines and dibutyryl cyclic AMP was reversible upon their
withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)